Blood Pressure in Treated Hypertensive Individuals With the
            <i>MTHFR</i>
            677TT Genotype Is Responsive to Intervention With Riboflavin

Wilson, Carol P.; McNulty, Helene; Ward, Mary; Strain, James J.; Trouton, Tom G.; Hoeft, Birgit; Weber, Peter; Roos, Franz F.; Horigan, Geraldine; McAnena, Liadhan; Scott, John M.

doi:10.1161/hypertensionaha.111.01047

Cited by 85 publications

(98 citation statements)

References 33 publications

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“…At baseline, 60% of the participants had failed to achieve target BP levels (≤140/90 mmHg), despite taking three or more antihypertensive medications. Following riboflavin intervention (1·6 mg/d for 16 weeks), systolic BP decreased significantly, a finding which confirmed that the BP-lowering effects of riboflavin in individuals with the MTHFR 677TT genotype were not confined to high-risk CVD patients but also applied to hypertensive individuals generally (51) .…”

Section: Mthfr 677c T Polymorphism and Blood Pressuresupporting

confidence: 57%

“…Given the known metabolic interdependencies between the relevant B-vitamins, work is underway at this Centre to investigate the independent and combined effects of riboflavin and folic acid on BP in hypertensive individuals with the TT genotype in a factorial study design. In addition, although convincing evidence has demonstrated the BP-lowering effects of low-dose riboflavin over a relatively short period of time (1·6 mg/16 weeks) (49)(50)(51) , it remains to be seen how variations in dose and duration would influence the BP-lowering effects of riboflavin in these genetically at-risk patients.…”

Section: Mthfr 677c T Polymorphism and Blood Pressurementioning

confidence: 99%

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MTHFR677TT genotype and disease risk: is there a modulating role for B-vitamins?

et al. 2013

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Methylenetetrahydrofolate reductase (MTHFR) is a critical folate-metabolising enzyme which requires riboflavin as its co-factor. A common polymorphism (677C→T) in the MTHFR gene results in reduced MTHFR activity in vivo which in turn leads to impaired folate metabolism and elevated homocysteine concentrations. Homozygosity for this polymorphism (TT genotype) is associated with an increased risk of a number of conditions including heart disease and stroke, but there is considerable variability in the extent of excess risk in various reports. The present review will explore the evidence which supports a role for this polymorphism as a risk factor for a number of adverse health outcomes, and the potential modulating roles for B-vitamins in alleviating disease risk. The evidence is convincing in the case which links this polymorphism with hypertension and hypertensive disorders of pregnancy, particularly preeclampsia. Furthermore, elevated blood pressure was found to be highly responsive to riboflavin intervention specifically in individuals with the MTHFR 677TT genotype. Future intervention studies targeted at these genetically predisposed individuals are required to further investigate this novel gene–nutrient interaction. This polymorphism has also been associated with an increased risk of neural tube defects (NTD) and other adverse pregnancy outcomes; however, the evidence in this area has been inconsistent. Preliminary evidence has suggested that there may be a much greater need for women with the MTHFR 677TT genotype to adhere to the specific recommendation of commencing folic acid prior to conception for the prevention of NTD, but this requires further investigation.

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Section: Mthfr 677c T Polymorphism and Blood Pressuresupporting

confidence: 57%

Section: Mthfr 677c T Polymorphism and Blood Pressurementioning

confidence: 99%

MTHFR677TT genotype and disease risk: is there a modulating role for B-vitamins?

et al. 2013

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“…Homozygosity (MTHFR 677TT genotype) for a common polymorphism in MTHFR, affecting over 10 % of the UK and Irish populations and up to 32 % of other populations worldwide (2) , has been associated with an increased risk of CVD (3) and more recently with hypertension (4) . Emerging evidence from intervention trials supports a novel role for riboflavin supplementation in protecting against hypertension specifically in individuals with the MTHFR 677TT genotype (5)(6)(7) . This genotypespecific effect of riboflavin potentially offers a personalised approach for the prevention and treatment of *Corresponding author: Professor M. Ward, email mw.ward@ulster.ac.uk…”

mentioning

confidence: 99%

Riboflavin status, MTHFR genotype and blood pressure: current evidence and implications for personalised nutrition

et al. 2016

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Clinical deficiency of the B-vitamin riboflavin (vitamin B 2 ) is largely confined to developing countries; however accumulating evidence indicates that suboptimal riboflavin status is a widespread problem across the developed world. Few international data are available on riboflavin status as measured by the functional biomarker, erythrocyte glutathione reductase activation coefficient, considered to be the gold standard index. One important role of riboflavin in the form of flavin dinucleotide is as a co-factor for the folate-metabolising enzyme methylenetetrahydrofolate reductase (MTHFR). Homozygosity for the common C677T polymorphism in MTHFR, affecting over 10 % of the UK and Irish populations and up to 32 % of other populations worldwide, has been associated with an increased risk of CVD, and more recently with hypertension. This review will explore available studies reporting riboflavin status worldwide, the interaction of riboflavin with the MTHFR C677T polymorphism and the potential role of riboflavin in personalised nutrition. Evidence is accumulating for a novel role of riboflavin as an important modulator of blood pressure (BP) specifically in individuals with the MTHFR 677TT genotype, with results from a number of recent randomised controlled trials demonstrating that riboflavin supplementation can significantly reduce systolic BP by 5-13 mmHg in these genetically at risk adults. Studies are however required to investigate the BP-lowering effect of riboflavin in different populations and in response to doses higher than 1·6 mg/d. Furthermore, work focusing on the translation of this research to health professionals and patients is also required.Riboflavin: Methylenetetrahydrofolate reductase: MTHFR C677T: Blood pressure:Personalised nutrition Riboflavin (vitamin B 2 ) is a water-soluble B-vitamin defined chemically as 7,8-dimethyl-10-1′-D-ribityl isoalloxazine. It acts as a precursor for FMN and FAD (1) . Clinical riboflavin deficiency is not generally considered to be a problem in the developed world but in recent years evidence has shown that sub-optimal status may be more widespread than generally perceived based on studies reporting the functional biomarker, erythrocyte glutathione reductase activation coefficient (EGRac) generally considered as the gold standard index of status. Few international data are however available based on EGRac and reports on riboflavin status are more commonly based solely on dietary intake data. Although riboflavin is required for numerous metabolic reactions its role (in the form of FAD) as a cofactor for the folatemetabolising enzyme, methylenetetrahydrofolate reductase (MTHFR) has recently received particular attention. Homozygosity (MTHFR 677TT genotype) for a common polymorphism in MTHFR, affecting over 10 % of the UK and Irish populations and up to 32 % of other populations worldwide (2) , has been associated with an increased risk of CVD (3) and more recently with hypertension (4) . Emerging evidence from intervention trials supports a novel role for riboflav...

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“…Hypertension and response to riboflavin [44,45] IsoP F2-isoprostanes † Risk of renal failure in hypertensives and cardiovascular risk [55,56] MPO Myeloperoxidase † , rs2333227…”

Section: Prkca Rs16960228mentioning

confidence: 99%

“…This raises the distinct possibility of using this or similar biomarkers, in personalized dietary programs and as a monitoring tool for dietary intake, including the use of functional foods, listed in Table 2 [43]. The MTHFR 677TT (rs1801133) variant is of particular interest in nutrigenomics as the folate pathway is modified with the administration vitamin B2 (riboflavin) [44,45]. A randomized trial, using genomic enrichment for hypertensive patients with the TT genotype, has shown that blood pressure can be reduced by approximately 6 mmHg systolic with administration of riboflavin [45].…”

Section: Metabolomics the Gut Microbiome And Nutrigeneticsmentioning

confidence: 99%

Personalized Hypertension Management in Practice

Gladding

Patrick²,

Manley³

et al. 2015

Per. Med.

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The revolution occurring in genomic and personalized medicine is likely to have a significant impact on the management of hypertension. However, from the perspective of translating new knowledge into clinical practice, progress has been slow. This review article summarizes recent advances in hypertension-related diagnostics while also offering new perspective on hypertension management for the future. Such new perspectives will likely require a paradigm shift toward more integrated and holistic approaches for better prevention and treatment of hypertension in both individuals and the population as a whole.

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Blood Pressure in Treated Hypertensive Individuals With the MTHFR 677TT Genotype Is Responsive to Intervention With Riboflavin

Cited by 85 publications

References 33 publications

MTHFR677TT genotype and disease risk: is there a modulating role for B-vitamins?

MTHFR677TT genotype and disease risk: is there a modulating role for B-vitamins?

Riboflavin status, MTHFR genotype and blood pressure: current evidence and implications for personalised nutrition

Personalized Hypertension Management in Practice

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